Investigators Discontinue Vibostolimab Combo in Extensive-Stage SCLC Trial

In the double-blind KeyVibe-008 trial, 460 patients were assigned to receive frontline vibostolimab/pembrolizumab plus chemotherapy or atezolizumab plus chemotherapy.

Investigators will discontinue their evaluation of a fixed-dose coformulation including vibostolimab plus pembrolizumab (Keytruda) in combination with chemotherapy for patients with extensive-stage small cell lung cancer (ES-SCLC) as part of the phase 3 KeyVibe-008 trial (NCT05224141), according to a press release from the developer, Merck.¹

Based on a pre-planned analysis, the data for overall survival (OS), the trial’s primary end point, fulfilled prespecified criteria for futility. Additionally, first-line treatment with the vibostolimab-based combination conferred a higher rate of adverse effects (AEs) and immune-related AEs vs atezolizumab (Tecentriq) in the comparator arm. Investigators are conducting a comprehensive analysis of these findings.

Patients enrolled on the KeyVibe-008 trial will be advised to halt treatment with vibostolimab/pembrolizumab and be offered the opportunity to switch to atezolizumab. Investigators intend to share their findings with the scientific community.

“[SCLC] remains a difficult disease to treat, as evident by the 7% 5-year survival rate and limited advancements in treatment options. Innovative research plays a critical role in improving our understanding to help patients achieve better outcomes, and while we hoped the results would be different, we remain committed to investigating novel approaches to treat this debilitating disease,” Marjorie Green, MD, senior vice president and head of oncology, global clinical development at Merck Research Laboratories, stated in the press release.¹

In the double-blind KeyVibe-008 trial, 460 patients were assigned to receive frontline vibostolimab/pembrolizumab plus chemotherapy or atezolizumab plus chemotherapy. Investigators administered pembrolizumab at 200 mg and vibostolimab at 200 mg intravenously every 3 weeks for 4 cycles in combination with etoposide plus carboplatin or cisplatin every 3 weeks for approximately 12 weeks followed by additional pembrolizumab/vibostolimab. In the comparator arm, patients received atezolizumab at 1200 mg every 3 weeks plus etoposide and carboplatin or cisplatin.

The trial’s primary end point was OS. Key secondary end points included progression-free survival, objective response rate, and duration of response based on blinded independent central review.

Patients 18 years and older with histologically or cytologically confirmed ES-SCLC defined as stage IV disease per American Joint Committee on Cancer, Eighth Edition were eligible for enrollment on the trial.² Other requirements for study entry included having measurable disease based on RECIST v1.1 guidelines and a predicted life expectancy of more than 3 months.

Those who had prior treatment for SCLC, a live or live-attenuated vaccine within 30 days of beginning study treatment, or a known additional malignancy requiring treatment within 3 years of entry were ineligible for enrollment. Patients were also unable to enroll if they had active autoimmune disease requiring systemic therapy within 2 years of entry, an active infection requiring systemic therapy, an allogeneic tissue or solid organ transplant, major surgery within 3 weeks of entry, or symptomatic ascites or pleural effusion.

Developers are also assessing treatment with fixed-dose vibostolimab/pembrolizumab in patients with lung cancer as part of the phase 3 KeyVibe-003 trial (NCT04738487), phase 3 KeyVibe-006 trial (NCT05298423), and phase 3 KeyVibe-007 trial (NCT05226598). These studies have not undergone any design modifications following interim external data monitoring committee safety reviews. Comprehensive safety monitoring is ongoing for these trials.

In May 2024, developers announced the discontinuation of the phase 3 KeyVibe-010 trial (NCT05665595) assessing adjuvant vibostolimab/pembrolizumab for patients with resected high-risk stage IIB to IV melanoma.³ The trial was terminated after the primary end point of recurrence-free survival reached the prespecified futility criteria based on a pre-planned analysis. Additionally, most patients receiving vibostolimab/pembrolizumab discontinued the therapy after immune-mediated AEs.

References

1. Merck provides update on phase 3 KeyVibe-008 trial evaluating an investigational fixed-dose combination of vibostolimab and pembrolizumab in patients with extensive- small cell lung cancer. News release. Merck. August 8, 2024. Accessed August 9, 2024. https://tinyurl.com/5fr4uwkt
2. Pembrolizumab/​vibostolimab (MK-7684A) or atezolizumab in combination with chemotherapy in first line treatment of extensive-stage small cell lung cancer (MK-7684A-008, KEYVIBE-008). ClinicalTrials.gov. Accessed August 9, 2024. https://tinyurl.com/yaupe59s
3. Merck provides update on phase 3 KeyVibe-010 trial evaluating an investigational coformulation of vibostolimab and pembrolizumab as adjuvant treatment for patients with resected high-risk melanoma. News release. Merck. May 13, 2024. Accessed August 9, 2024. https://tinyurl.com/2zeefcj2